Curcumin, a potent natural anti-oxidant and anti-inflammatory agent, has shown therapeutic potential against many diseases. These include cancers (colon, prostate, breast, skin, leukemia, etc.), atherosclerosis, stroke, CNS alcohol toxicity, traumatic brain injury, Huntington's disease, Marie-Charcot Tooth, multiple sclerosis and Alzheimer's disease.
Curcumin in this specification is referred as total curcuminoids containing curcumin, desmethoxycurcumin and bis-desmethoxycurcumin.
Curcumin is a crystalline compound and poorly soluble in water at pH less than 7. Major reasons contributing to the lower plasma and tissue levels of curcumin are due to poor absorption, high first pass metabolism and rapid systemic elimination. Most of the curcumin is not absorbed and simply passes through the GI tract and is excreted. Garcea, G. et al. (2004) reported that patients taking 3.6 g of curcumin a day (as a standard powder supplied by Sabinsa Corporation), drug levels in blood and liver were found to be negligible.
Curcumin is not soluble at acidic pH and breaks down in solution at neutral or alkaline pH (e.g., in the GI tract, after the small intestine), In addition, curcumin is susceptible to rapid glucuronidation/sulfation.
WO2007103435 discloses the compositions comprising curcuminoid, antioxidant (to stabilize curcumin against hydrolysis), water-soluble pharmaceutically acceptable carrier and optionally glucuronidation inhibitor. The said formulation with 35% w/w curcumin resulted in improved bioavailability.
CN100352430C discloses self-micro-emulsified curcumin preparation comprising curcumin, surfactant, co-surfactant, oil phase and solid adsorbent providing self-micro-emulsified system having liquid drops with size below 100 nm. Such compositions show increase in curcumin solubility and absorption in gastrointestinal tract with higher bioavailability. The concentration of curcumin in composition is in the range of 0.33 to 1.56% w/v.
WO2010010431 discloses self nano-emulsion compositions comprising curcumin (0.1 to 10% w/w), a lipidic carrier system with a hydrophilic-lipophilic balance (HLB) between 3 to 14 and a pH buffer. The lipidic carrier system is selected from one or more mono- and di-esters of saturated or unsaturated long chain fatty acids with low and medium molecular weight polyoxyethylene glycerol ethers or combinations thereof. The composition further comprises molecular aggregation inhibitor(s), a surface active agent and a co-solvent. The group of excipients used as lipidic carrier system belongs to alkyl-glycerol ether surfactants category (M. J. Lawrence et. al. Chemistry and Physics of Lipids, Volume 82, Issue 2, 19 Aug. 1996, Pages 89-100) that led to increase in overall surfactant concentration up to 90% of the formulation. The higher concentration of surfactants in the formulation is undesirable as they are likely to cause gastric irritation and gastric mucosal damage.
There is an unmet need to develop stable liquid pharmaceutical composition of curcumin or its pharmaceutically acceptable salts or its derivatives with higher curcumin concentration, without using acid buffer and/or molecular aggregation inhibitor(s) and without using high concentration of surfactants.